B cells are associated with survival and immunotherapy response in sarcoma

Abstract

Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes^1,2. The clinical presentation of patients with different subtypes is often atypical, and responses to therapies such as immune checkpoint blockade vary widely^3,4. To explain this clinical variability, here we study gene expression profiles in 608 tumours across subtypes of soft-tissue sarcoma. We establish an immune-based classification on the basis of the composition of the tumour microenvironment and identify five distinct phenotypes: immune-low (A and B), immune-high (D and E), and highly vascularized (C) groups. In situ analysis of an independent validation cohort shows that class E was characterized by the presence of tertiary lymphoid structures that contain T cells and follicular dendritic cells and are particularly rich in B cells. B cells are the strongest prognostic factor even in the context of high or low CD8⁺ T cells and cytotoxic contents. The class-E group demonstrated improved survival and a high response rate to PD1 blockade with pembrolizumab in a phase 2 clinical trial. Together, this work confirms the immune subtypes in patients with soft-tissue sarcoma, and unravels the potential of B-cell-rich tertiary lymphoid structures to guide clinical decision-making and treatments, which could have broader applications in other diseases.

Keywords

Affiliated Institutions

• Université Paris Cité FR
• University of Pittsburgh US
• Inserm FR
• Sorbonne Université FR
• Institut Gustave Roussy FR
• National Taiwan University TW
• Institut Bergonié FR
• The University of Texas MD Anderson Cancer Center US
• Centre de Recherche des Cordeliers FR
• La Ligue Contre le Cancer FR
• Sarcoma Alliance for Research through Collaboration US
• Sorbonne Paris Cité FR
• National Taiwan University Hospital TW
• Cancer Research And Biostatistics US

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